2. Academic Validation
  3. SARS-CoV-2 Membrane Protein Inhibits Type I Interferon Production Through Ubiquitin-Mediated Degradation of TBK1

SARS-CoV-2 Membrane Protein Inhibits Type I Interferon Production Through Ubiquitin-Mediated Degradation of TBK1

  • Front Immunol. 2021 May 18;12:662989. doi: 10.3389/fimmu.2021.662989.
Liyan Sui 1,  Yinghua Zhao 1,  Wenfang Wang 2,  Ping Wu 3,  Zedong Wang 1,  Yang Yu 4,  Zhijun Hou 3,  Guangyun Tan 5,  Quan Liu 1 6
Affiliations

Affiliations

  • 1 Laboratory of Emerging Infectious Disease, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, China.
  • 2 College of Basic Medical Science, Jilin University, Changchun, China.
  • 3 College of Wildlife and Protected Area, Northeast Forestry University, Harbin, China.
  • 4 Hospital of Stomatology, Jilin University, Changchun, China.
  • 5 Department of Immunology, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, China.
  • 6 School of Life Sciences and Engineering, Foshan University, Foshan, China.
PMID: 34084167 DOI: 10.3389/fimmu.2021.662989
Abstract

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative pathogen of current COVID-19 pandemic, and insufficient production of type I interferon (IFN-I) is associated with the severe forms of the disease. Membrane (M) protein of SARS-CoV-2 has been reported to suppress host IFN-I production, but the underlying mechanism is not completely understood. In this study, SARS-CoV-2 M protein was confirmed to suppress the expression of IFNβ and interferon-stimulated genes induced by RIG-I, MDA5, IKKϵ, and TBK1, and to inhibit IRF3 phosphorylation and dimerization caused by TBK1. SARS-CoV-2 M could interact with MDA5, TRAF3, IKKϵ, and TBK1, and induce TBK1 degradation via K48-linked ubiquitination. The reduced TBK1 further impaired the formation of TRAF3-TANK-TBK1-IKKε complex that leads to inhibition of IFN-I production. Our study revealed a novel mechanism of SARS-CoV-2 M for negative regulation of IFN-I production, which would provide deeper insight into the innate immunosuppression and pathogenicity of SARS-CoV-2.

Keywords

SARS-CoV-2; TBK1; membrane protein; type I interferon; ubiquitination.

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